The value and correlation between PRL‐3 expression and matrix metalloproteinase activity and expression in human gliomas

Abstract

Local invasion of tumor cells is characteristic of most human glioma invasions. It is associated with increased motility and a potential to degrade the extracellular matrix. Matrix metalloproteinases (MMPs) have been proved to be a main process in local invasion of brain tumor. PRL-3 is a new protein tyrosine phosphatase which would also degrade the extracellular matrix and has been proved to be expressed in liver metastases derived from colorectal cancer. In this study, we sought to investigate the expression of PRL-3 in glioma tissues and investigate the relationship between MMPs (MMP2, MMP9, membrane-type matrix metalloproteinase 1 [MT1-MMP]) activity and expression in gliomas. The modifications of in situ hybridization of mRNA phosphatase of regenerating liver-3 (PRL-3) methods are preformed in the study of paraffin-embedded slides. The immunohistochemistry and gelatin zymography are used to detect the expression of PRL-3 and activity of MMPs. The results show that PRL-3 mRNA and antibody of PRL-3 are detected in glioma tissues mainly in grades IV and III, only a little in grade II, but not in normal brain tissue and glioma grade I. MMP2 and MMP9 are observed mainly in glioma tissues of grades IV and III in activity and expression. MT1-MMP protein is located in glioma tissues and vessel endothelial cells. This is the first report of detecting PRL-3 expression in gliomas, especially in grades III and IV, which may play an important role in progression of gliomas. PRL-3, MMP2 and MT1-MMP cooperatively contribute to gliomas invasion. Intermediate MMP2 (MT1-MMP, TIMP-2, MMP2 trimeric complex) is detected in high grades of glioma tissues by gelatin zymography and may be a marker indicating latent malignance of gliomas.

Phosphatase of regenerating liver‐3 promotes migration and invasion by upregulating matrix metalloproteinases‐7 in human colorectal cancer cells

“…PRL-3 is amplified and overexpressed in CRC metastases compared with primary tumors, and its expression correlates with metastasis in other tumor types. 8,[11][12][13][14][15][16] In this report, PRL-3 induced cell migration and invasion in a human colon cancer-derived cell system (DLD-1 cells) and enhanced DLD-1 cell motility. It is consistent with previous studies with other cancer cell lines.…”

“…This result is consistent with previous reports showing that the function and localization of PRL-3 can be inhibited by FPTase inhibitors and regulated by MMP expression in other cell types. 3 Although it has been reported that MMP-2 and -14 cooperatively contribute to PRL-3-dependent invasion of gliomas, 16 the expression level of MMP-14 mRNA was very high, and its expression was dramatically downregulated by the FPTase inhibitor in DLD-1 (PRL-3) cells. However, overexpression of MMP-14 in the cells did not effect on migration of the cells.…”

“…It has been shown to be expressed in liver metastases derived from CRC. 16 Among more than 20 MMPs, matrilysin (MMP-7) appears to be one of the most important MMPs in human colon cancers, because it is highly overexpressed in colon cancer. 17,18 The mechanisms by which PRL PTPs promote these phenotypes have not yet been elucidated.…”

The Role of Matrix Metalloproteinases a nd Tissue Inhibitors of Metalloproteinases in the Progression of Astrocytomas

“…This activity has been documented both in vivo and in vitro (Martin & Matrisian, 2007). The pro-invasive activity of MT1-MMP has been associated by some authors with invasion and progression in other tumors, such as neck tumors by Zhai et al (2005) and astrocytic tumors by Forsyth et al (1999);Nakada et al (1999Nakada et al ( , 2001 and Kong et al (2007). Among the studies that have found a direct relationship between the increased expression of MT1-MMP and the evolution of gliomas, that of Nuttall et al (2003) stands out because it found a greater than 21-fold increase in the level of MT1-MMP mRNA in glioblastomas relative to non-tumor brain tissue.…”

Phosphatase of regenerating liver-3 as a prognostic biomarker in histologically node-negative gastric cancer

“…Among human tumor tissues, PRL-3 was first identified to be specifically overexpressed in liver metastases derived from colorectal cancer using serial analysis of gene expression (SAGE) technology (9), and subsequently an accumulating number of studies demonstrated PRL-3 overexpression in various tumor types (10)(11)(12)(13)(14). Enforced PRL-3 expression can promote invasion, migration, and angiogenesis in cell culture and mouse model systems (15)(16)(17)(18)(19), whereas knockdown of endogenous PRL-3 by small interfering RNA (siRNA) or transfection with catalytically inactive mutants can abrogate these properties (11,20,21).…”